tbuckley/cabot-search huggingface dataset:
Rethinking the immunotherapy numbers game
Authors: Rebecca A Bekker, Mohammad U Zahid, Jennifer M Binning, Bryan Q Spring, Patrick Hwu, Shari Pilon-Thomas, Heiko Enderling
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immunotherapies are a major breakthrough in oncology, yielding unprecedented response rates for some cancers. Especially in combination with conventional treatments or targeted agents, immunotherapeutics offer invaluable tools to improve outcomes for many patients. However, why not all patients have a favorable response remains unclear. There is an increasing appreciation of the contributions of the complex tumor microenvironment, and the tumor-immune ecosystem in particular, to treatment outcome. To date, however, there exists no immune biomarker to explain why two patients with similar clinical stage and molecular profile would have different treatment outcomes. We hypothesize that it is critical to understand both the immune and tumor states to understand how the complex system will respond to treatment. Here, we present how integrated mathematical oncology approaches can help conceptualize the effect of various immunotherapies on a patient's tumor and local immune environment, and how combinations of immunotherapy and cytotoxic therapy may be used to improve tumor response and control and limit toxicity on a per patient basis.
Clip with rubber band modification for dynamic traction in colonic endoscopic submucosal dissection
Authors: Joana Alves Silva, Daniela Falcão, Sofia Ponte, Ricardo Marcos-Pinto, Isabel Pedroto, Ricardo Küttner-Magalhães
Journal: Endoscopy (2022)

A 63-year-old-woman was referred because of a 40-mm laterally-spreading tumor, nongranular type (LST-NG), Paris 0-Is + IIa, JNET type 2B, in the descending colon, with a tattoo beneath it, consistent with a residual lesion following a previous resection. Endoscopic submucosal dissection (ESD) was initiated with a partial mucosal incision ([Video 1]). Difficulty was experienced in exposing the submucosal layer, even with the pocket-creation method and an underwater strategy.
Neurodevelopment at 5 Years of Age According to Early Screening for Patent Ductus Arteriosus in Extremely Preterm Infants
Authors: Gilles Cambonie, Jean-Christophe Rozé, Laetitia Marchand-Martin, Stéphane Marret, Xavier Durrmeyer, Héloïse Torchin, Pierre-Yves Ancel
Journal: JAMA (2022)

This study compares neurodevelopment at 5 years of age in children who were extremely preterm infants and who underwent early systematic echocardiographic screening for patent ductus arteriosus (PDA) vs those who did not undergo screening.
Monkeypox: Symptoms seen in London sexual health clinics differ from previous outbreaks, study finds
Authors: Melina Zachariou
Journal: BMJ (2022)

Monkeypox: Symptoms seen in London sexual health clinics differ from previous outbreaks, study finds Melina ZachariouMonkeypox symptoms seen in patients four sexual health clinics in London appear to differ from those seen in previous outbreaks in Nigeria, Sudan, and the US, a study has found.
Association of the “Weekend Warrior” and Other Leisure-time Physical Activity Patterns With All-Cause and Cause-Specific Mortality
Authors: Mauricio dos Santos, Gerson Ferrari, Dong Hoon Lee, Juan Pablo Rey-López, Dagfinn Aune, Bing Liao, Wentao Huang, Jing Nie, Yafeng Wang, Edward Giovannucci, Leandro F. M. Rezende
Journal: JAMA Internal Medicine (2022)

It is unclear whether the weekly recommended amount of moderate to vigorous physical activity (MVPA) has the same benefits for mortality risk when activity sessions are spread throughout the week vs concentrated in fewer days.To examine the association of weekend warrior and other patterns of leisure-time physical activity with all-cause and cause-specific mortality.This large nationwide prospective cohort study included 350 978 adults who self-reported physical activity to the US National Health Interview Survey from 1997 to 2013. Participant data were linked to the National Death Index through December 31, 2015.Participants were grouped by self-reported activity level: physically inactive (<150 minutes per week [min/wk] of MVPA) or physically active (≥150 min/wk of moderate or ≥75 min/wk of vigorous activity). The active group was further classified by pattern: weekend warrior (1-2 sessions/wk) or regularly active (≥3 session/wk); and then, by frequency, duration/session, and intensity of activity.All-cause, cardiovascular disease (CVD), and cancer mortality. Statistical analyses were performed in April 2022.A total of 350 978 participants (mean [SD] age, 41.4 [15.2] years; 192 432 [50.8%] women; 209 432 [67.8%] Non-Hispanic White) were followed during a median of 10.4 years (3.6 million person-years). There were 21 898 deaths documented, including 4130 from CVD and 6034 from cancer. Compared with physically inactive participants, hazard ratios (HR) for all-cause mortality were 0.92 (95% CI, 0.83-1.02) for weekend warrior and 0.85 (95% CI, 0.83-0.88) for regularly active participants; findings for cause-specific mortality were similar. Given the same amount of total MVPA, weekend warrior participants had similar all-cause and cause-specific mortality rates as regularly active participants. The HRs for weekend warrior vs regularly active participants were 1.08 (95% CI, 0.97-1.20) for all-cause mortality; 1.14 (95% CI, 0.85-1.53) for CVD mortality; and 1.07 (95% CI, 0.87-1.31) for cancer mortality.The findings of this large prospective cohort study suggest that individuals who engage in active patterns of physical activity, whether weekend warrior or regularly active, experience lower all-cause and cause-specific mortality rates than inactive individuals. Significant differences were not observed for all-cause or cause-specific mortality between weekend warriors and regularly active participants after accounting for total amount of MVPA; therefore, individuals who engage in the recommended levels of physical activity may experience the same benefit whether the sessions are performed throughout the week or concentrated into fewer days.
Fluoroscopic balloon dilatation with antegrade and retrograde endoscopes is useful for complete pharyngoesophageal obstruction after radiation therapy
Authors: Gozo Fukushi, Ai Fujimoto, Kenzo Hara, Yusuke Nishikawa, Takahisa Matsuno, Takahisa Matsuda, Yoshinori Igarashi
Journal: Endoscopy (2022)

Radiation therapy for pharyngoesophageal cancer can lead to severe esophageal stricture in the irradiation field [1]. Balloon dilation is often the primary mode of treatment [2]; however, in cases with severe stenosis, dilation using antegrade and retrograde endoscopes is useful [3] [4]. However, it may also increase the risk of esophageal perforation [5]. Herein we report a case of fluoroscopic balloon dilation with double endoscopes that was successful for dilating a complete pharyngoesophageal obstruction due to chemoradiation therapy.
Fear of the GMC significantly hinders the GP workforce
Authors: Bob Hodges
Journal: BMJ (2022)

Acute retinal necrosis (ARN) is a clinical syndrome featuring severe vitritis and occlusive vasculitis characterised by full thickness necrotising retinitis. ARN is usually caused by an acute infection by either varicella zoster virus or herpes simplex virus, rarely cytomegalovirus (CMV). ARN often occurs in healthy adults; occasionally affecting immunocompromised patients with poor prognosis including significant visual loss and detachment of the atrophic retina regardless of antiviral treatment. We presented a man in his early 30s with a history of left eye floaters and blurred vision. He was diagnosed with T-cell acute lymphoblastic leukaemia 1 year ago and treated with chemotherapy and allogenic haematopoietic stem cell transplant 5 months ago. His clinical diagnosis was left eye ARN caused by acute viral infection with CMV being the most likely cause, which is rarely seen in immunocompromised patients. Our case highlighted a diagnostic and therapeutic challenge in the absence of guideline or evidence-based literature to follow.
The Elephant Evolved p53 Isoforms that Escape MDM2-Mediated Repression and Cancer
Authors: Monikaben Padariya, Mia-Lyn Jooste, Ted Hupp, Robin Fåhraeus, Borek Vojtesek, Fritz Vollrath, Umesh Kalathiya, Konstantinos Karakostis
Journal: Molecular Biology and Evolution (2022)

Abstract The p53 tumor suppressor is a transcription factor with roles in cell development, apoptosis, oncogenesis, aging, and homeostasis in response to stresses and infections. p53 is tightly regulated by the MDM2 E3 ubiquitin ligase. The p53–MDM2 pathway has coevolved, with MDM2 remaining largely conserved, whereas the TP53 gene morphed into various isoforms. Studies on prevertebrate ancestral homologs revealed the transition from an environmentally induced mechanism activating p53 to a tightly regulated system involving cell signaling. The evolution of this mechanism depends on structural changes in the interacting protein motifs. Elephants such as Loxodonta africana constitute ideal models to investigate this coevolution as they are large and long-living as well as having 20 copies of TP53 isoformic sequences expressing a variety of BOX-I MDM2-binding motifs. Collectively, these isoforms would enhance sensitivity to cellular stresses, such as DNA damage, presumably accounting for strong cancer defenses and other adaptations favoring healthy aging. Here we investigate the molecular evolution of the p53–MDM2 system by combining in silico modeling and in vitro assays to explore structural and functional aspects of p53 isoforms retaining the MDM2 interaction, whereas forming distinct pools of cell signaling. The methodology used demonstrates, for the first time that in silico docking simulations can be used to explore functional aspects of elephant p53 isoforms. Our observations elucidate structural and mechanistic aspects of p53 regulation, facilitate understanding of complex cell signaling, and suggest testable hypotheses of p53 evolution referencing Peto’s Paradox.
Electrohydraulic lithotripsy using peroral cholangioscopy for impaction of stent-stone complex around biliary plastic stent
Authors: Yuta Tanimoto, Shota Harai, Mitsuharu Fukasawa, Ei Takahashi, Shinichi Takano, Nobuyuki Enomoto
Journal: Endoscopy (2022)

A stent-stone complex is a rare complication of long-term placement of biliary plastic stents [1] [2]. Stones form around the proximal end of the stent, making endoscopic removal of the stent difficult. Herein we report a case of successful endoscopic removal of a stent-stone complex using peroral cholangioscopy-guided electrohydraulic lithotripsy (EHL).
What Is Dry Eye Disease?
Authors: Kristin Walter
Journal: JAMA (2022)

Takenori Inomata, MD, PhD, MBA; Masao Iwagami, MD, PhD, MSc, MPH; Masahiro Nakamura, MD, PhD; Tina Shiang, MD; Yusuke Yoshimura; Keiichi Fujimoto, MD; Yuichi Okumura, MD; Atsuko Eguchi; Nanami Iwata; Maria Miura, MD; Satoshi Hori, MD, PhD; Yoshimune Hiratsuka, MD, PhD, MPH; Miki Uchino, MD, PhD, MPH; Kazuo Tsubota, MD, PhD; Reza Dana, MD, MPH, MSc; Akira Murakami, MD, PhD
Sustained Oncogenic Signaling in the Cytostatic State Enables Targeting of Nonproliferating Persistent Cancer Cells
Authors: Lisa M. Kim, Paul Y. Kim, Yemarshet K. Gebreyohannes, Cheuk T. Leung
Journal: Cancer Research (2022)

Abstract Many advanced therapeutics possess cytostatic properties that suppress cancer cell growth without directly inducing death. Treatment-induced cytostatic cancer cells can persist and constitute a reservoir from which recurrent growth and resistant clones can develop. Current management approaches primarily comprise maintenance and monitoring because strategies for targeting nonproliferating cancer cells have been elusive. Here, we used targeted therapy paradigms and engineered cytostatic states to explore therapeutic opportunities for depleting treatment-mediated cytostatic cancer cells. Sustained oncogenic AKT signaling was common, while nonessential, in treatment-mediated cytostatic cancer cells harboring PI3K-pathway mutations, which are associated with cancer recurrence. Engineering oncogenic signals in quiescent mammary organotypic models showed that sustained, aberrant activation of AKT sensitized cytostatic epithelial cells to proteasome inhibition. Mechanistically, sustained AKT signaling altered cytostatic state homeostasis and promoted an oxidative and proteotoxic environment, which imposed an increased proteasome dependency for maintaining cell viability. Under cytostatic conditions, inhibition of the proteasome selectively induced apoptosis in the population with aberrant AKT activation compared with normal cells. Therapeutically exploiting this AKT-driven proteasome vulnerability was effective in depleting treatment-mediated cytostatic cancer cells independent of breast cancer subtype, epithelial origin, and cytostatic agent. Moreover, transient targeting during cytostatic treatment conditions was sufficient to reduce recurrent tumor growth in spheroid and mouse models. This work identified an AKT-driven proteasome-vulnerability that enables depletion of persistent cytostatic cancer cells harboring PTEN–PI3K pathway mutations, revealing a viable strategy for targeting nonproliferating persistent cancer cell populations before drug resistance emerges. Significance: This study finds that sustained oncogenic signaling in therapy-induced cytostatic cancer cells confers targetable vulnerabilities to deplete persistent cancer cell populations and reduce cancer recurrence.
A safe needle-knife precut papillotomy technique in a patient with a naïve papilla and surgically altered anatomy
Authors: Kunihiro Hosono, Shin Yagi, Yusuke Kurita, Sho Hasegawa, Takamitsu Sato, Kensuke Kubota, Atsushi Nakajima
Journal: Endoscopy (2022)

Cannulation of the biliary duct during endoscopic retrograde cholangiopancreatography (ERCP) in patients with a naïve papilla who have surgically altered anatomy, such as a Roux-en-Y anastomosis, remains difficult. The ERCP technique known as needle-knife precut papillotomy [1] is difficult to perform in patients with surgically altered anatomy because of the abnormal axis of the bile duct and a risk of intestinal perforation. Here, we present a safe freehand needle-knife precut papillotomy technique in a patient with surgically altered anatomy.
An international Delphi consensus regarding best practice recommendations for hyperkalaemia across the cardiorenal spectrum
Authors: James O. Burton, Andrew J.S. Coats, Csaba P. Kovesdy, Biff F. Palmer, Ileana L. Piña, Giuseppe Rosano, Manish M. Sood, Shelley Zieroth
Journal: European Journal of Heart Failure (2022)
Charting the meningeal lymphatic network
Authors: Sandro Da Mesquita
Journal: The Journal of Experimental Medicine (2022)

A genuine network of lymphatic vessels can be found in the dural layer of the meninges that ensheathe the brain and spinal cord of mammalians. In this issue, Jacob et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220035) employ light sheet fluorescence imaging of intact mouse heads to provide a more comprehensive chart of the meningeal lymphatic vasculature and draw a parallel between lymphatic drainage of cerebrospinal fluid in mice and humans.
Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections
Authors: Yizhuo Wang, Shuyun Liu, Lan Li, Ling Li, Xueli Zhou, Meihua Wan, Peng Lou, Meng Zhao, Ke Lv, Yujia Yuan, Younan Chen, Yanrong Lu, Jingqiu Cheng, Jingping Liu
Journal: Journal of Controlled Release (2022)
Corticostriatal circuits in the transition to chronic back pain: The predictive role of reward learning
Authors: Martin Löffler, Seth M. Levine, Katrin Usai, Simon Desch, Mina Kandić, Frauke Nees, Herta Flor
Journal: Cell Reports Medicine (2022)

Connectivity between the nucleus accumbens (NAc) and ventromedial prefrontal cortex (vmPFC) and reward learning independently predict the transition from acute to chronic back pain (CBP). However, how these predictors are related remains unclear. Using functional magnetic resonance imaging, we investigate NAc- and vmPFC-dependent reward learning in 50 patients with subacute back pain (SABP) and follow them over 6 months. Additionally, we compare 29 patients with CBP and 29 pain-free controls to characterize mechanisms of reward learning in the chronic stage. We find that the learning-related updating of the value of reinforcement (prediction error) in the NAc predicts the transition to chronicity. In CBP, compared with controls, vmPFC responses to this prediction error signal are decreased, but increased during a discriminative stimulus. Distinct processes of reward learning in the vmPFC and NAc characterize the development and maintenance of CBP. These could be targeted for the prevention and treatment of chronic pain.
Bread loaf sections provide useful information on more than 0·5% of surgical margins
Authors: Melissa M. Warne, Matthew M. Klawonn, Robert T. Brodell
Journal: British Journal of Dermatology (2022)

It is often quoted that classic bread-loaf sectioning of excisional specimens assesses 0.5% of the margin, but careful mathematical analysis reveals that bread-loaf sectioning appraises far more than that and is an effective and economical means to check margins.
How Can We Improve Surgical Care of Patients Who Are Homeless?
Authors: Mary Kathryn Abel, Joseph A. Lin, Elizabeth C. Wick
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Kids Move Much More When Screen Time Is Reduced
Authors: Anita Slomski
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Urgency of Now and the Responsibility to Do More—My Commitment for <i>JAMA</i> and the JAMA Network
Authors: Kirsten Bibbins-Domingo
Journal: JAMA (2022)

Kirsten Bibbins-Domingo, PhD, MD, MAS; Annette Flanagin, MA, RN; Stacy L. Christiansen, MA; Greg Curfman, MD
The NCF1 variant p.R90H aggravates autoimmunity by facilitating the activation of plasmacytoid dendritic cells
Authors: Yao Meng, Jianyang Ma, Chao Yao, Zhizhong Ye, Huihua Ding, Can Liu, Jun Li, Guanhua Li, Yuke He, Jia Li, Zhihua Yin, Li Wu, Haibo Zhou, Nan Shen
Journal: Journal of Clinical Investigation (2022)

Plasmacytoid dendritic cells (pDCs) are a professional type I IFN producer that play critical roles in the pathogenesis of autoimmune diseases. However, both genetic regulation of the function of pDCs and their relationships with autoimmunity are largely undetermined. Here, we investigated the causality of the neutrophil cytosolic factor 1 (NCF1) missense variant, which is one of the most significant associated risk variants for lupus, and found that the substitution of arginine (R) for histidine (H) at position 90 in the NCF1 protein (NCF1 p.R90H) led to excessive activation of pDCs. A mechanism study demonstrated that p.R90H reduced the affinity of NCF1 for phospholipids, thereby impairing endosomal localization of NCF1. As NCF1 is a subunit of the NADPH oxidase 2 (NOX2) complex, this impairment led to an acidified endosomal pH and facilitated downstream TLR signaling. Consistently, the homozygous knockin mice manifested aggravated lupus progression in a pDC-dependent lupus model. More important, pharmaceutical intervention revealed that hydroxychloroquine (HCQ) could antagonize the detrimental function of NCF1 p.R90H in the lupus model and systemic lupus erythematosus samples, supporting the idea that NCF1 p.R90H could be identified as a genetic biomarker for HCQ application. Therefore, our study provides insights into the genetic control of pDC function and a paradigm for applying genetic variants to improve targeted therapy for autoimmune diseases.